The Center for Research on the Etiology and Treatment of Alcohol Dependence is dedicated to the systematic examination of the nature, development, and clinical management of alcohol-use disorders. The Center is organized around an integrated network of three basic science laboratories (Neurobiology, Neurodynamics, and Psychophysiology) and one treatment evaluation laboratory which incorporates basic science methods and concepts into its program. During the next five-year grant period we propose to initiate a multidisciplinary program of laboratory studies and treatment evaluation research within four major research components. Research Component I involves four studies of promising clinical interventions, including new pharmacotherapies (serotonin uptake inhibitors and nonbenzodiazapine anxiolytics), manual-guided cognitive-behavioral therapy, cue exposure conditioning therapy, and psychotherapy. Component II consists of three laboratory-based studies designed to clarify the relationship between alcohol dependence and biological responses to alcohol-related stimuli in human subjects. We also propose to initiate animal studies to clarify results of our human research with respect to conditioned neuroendocrine responses as factors affecting alcohol consumption. The third research component will focus on antisocial personality (ASP) and family history as risk factors for alcohol dependence. An ongoing longitudinal prospective study of genetic and environmental vulnerability factors will be continued in a cohort study of young adult offspring of alcoholics during the period of maximum risk for alcohol dependence. Two additional studies will examine putative risk factors (ASP, family history and temperament) in relation to measures of CNS functioning and psychophysiological responsiveness to alcohol-related cues. Component IV will examine the disposition of ethanol in biological membranes at the angstrom level by using x-ray and neutron diffraction techniques. This high resolution approach will be correlated with functional markers of membrane receptors and enzymes. Ultimately, these techniques will be tested on human biological membranes to determine whether genetic susceptibility to alcoholism or long-term alcohol use per se alters membranes in a measurable way.